Patients undergoing hemodialysis in the United States have high rates of mortality and morbidity. This, in part, is probably due to the delivery of insufficient amounts of dialysis treatment. The determination of an adequate quantity of therapy (Kt/V = 1.0) was generated from data of the National Cooperative Dialysis Study (NCDS). The technology and subjects studied at the time of the NCDS do not adequately reflect current conditions. Hemodialysis can now be performed more efficiently, anemia can be corrected, and there is an availability of high-flux/biocompatible dialyzers. Patients are now older, and there is a high proportion of diabetic patients. The optimal hemodialysis treatment for the current population or patients is unknown. The aim of this proposal is to carry out a cooperative multi-center clinical trial, Mortality and Morbidity in Hemodialysis (MMHD), with the goal of determining the effects of dialysis intensity and dialyzer type on mortality (primary outcome) and morbidity (secondary outcome). Fifteen centers will each enroll and maintain 60 patients in the study. Their demographic and clinical status should reflect those of the general dialysis population. They will be randomized into four treatment groups to address the following specific aims: to determine if maintaining a Kt/V of 1.4 (range 1.3-1.5) confers lower rates of mortality and morbidity compared to a Kt/V of 1.0 (range 0.9-1.1) in hemodialysis patients; to evaluate whether the use of high- flux/biocompatible dialyzers is associated with less mortality and morbidity than cuprophane dialyzers; and to assess if the more aggressive interventions are safe and acceptable to patients. This large study will require high quality data collection and uniform standards of care among all participating dialysis centers. If these specific aims are fulfilled a more rational and effective strategy to optimally treat hemodialysis patients will be devised and implemented.